Complex Injectable Formulations and Their Applications

Complex injectables

Formulations requiring special physicochemical properties.

Physicochemical properties

Characteristics like solubility, stability, and viscosity.

Solubility

Ability of a substance to dissolve in a solvent.

Stability

Resistance to degradation over time and conditions.

Viscosity

Thickness or resistance to flow of a liquid.

Excipients

Inactive substances used to aid drug formulation.

Stabilizers

Agents that enhance the stability of formulations.

Adverse reactions

Unintended harmful effects from drug administration.

Product quality

Consistency and reliability of pharmaceutical products.

Modified release

Controlled release of drug over time.

Parenteral products

Drugs delivered via injection, bypassing the digestive tract.

Long-Acting Injectable (LAI)

Injectables designed for prolonged therapeutic effect.

NDA pathway

New Drug Application process for FDA approval.

In Vitro Release

Testing drug release in a controlled environment.

Aqueous crystalline drug suspensions

Suspensions containing solid drug particles in liquid.

Aripiprazole

Antipsychotic medication used for schizophrenia treatment.

Abilify Maintena Kit

LAI formulation of aripiprazole for schizophrenia.

Medroxyprogesterone acetate

Hormonal drug used for contraception.

Depo-Provera

LAI contraceptive with 3-month efficacy.

Paliperidone palmitate

LAI antipsychotic for schizophrenia with extended release.

Invega Trinza

LAI formulation for schizophrenia with 3-month duration.

Approval date

Date when a drug receives regulatory approval.

Exenatide

Synthetic drug for Type 2 diabetes management.

Bydureon

Exenatide formulation, 2 mg weekly, SC administration.

Bydureon Pen

Pre-filled pen for Bydureon, 2 mg weekly, SC.

Bydureon Bsice

Bydureon variant, 2 mg in 0.85 mL, SC.

Leuprolide acetate

Hormone therapy for prostatic cancer treatment.

Lupron Depot

Leuprolide formulation, 3.75 mg monthly, IM.

Lupron Depot-Ped

Leuprolide for central precocious puberty, IM.

Minocycline HCl

Antibiotic for periodontitis, 1 mg base variable.

Naltrexone

Medication for alcohol dependence, 380 mg monthly.

Octreotide acetate

Acromegaly treatment, varying doses every four weeks.

Pasireotide pamoate

Acromegaly and Cushing's disease treatment, IM.

Risperidone

Antipsychotic for schizophrenia, varying doses, IM.

Triamcinolone acetonide

Osteoarthritis pain relief, 32 mg every 3 months.

Triptorelin pamoate

Prostate cancer treatment, varying doses, IM.

Triptodur Kit

Central precocious puberty treatment, 22.5 mg, IM.

Buprenorphine

Opioid disorder treatment, 100 mg/0.5 ml monthly.

Degarelix acetate

Prostate cancer treatment, 80 mg every 28 days.

Doxycycline hyclate

Antibiotic for periodontal disease, 50 mg subgingival.

Lanreotide acetate

Acromegaly treatment, varying doses every 4 weeks.

Goserelin acetate

Prostatic cancer treatment, 3.6 mg every 28 days.

Modified injectables

Insoluble drugs in emulsion for local effect.

Modified release injectables

Sustained release for chronic administration, reduced frequency.

Long-acting injectables (LAIs)

Sustained drug release for prolonged therapeutic effect.

Sustained-release formulation

Delivers drugs over extended periods, enhancing efficacy.

Injection frequency

Reduced number of injections improves patient adherence.

Cost-effectiveness

Lower dosing reduces overall drug expenses.

Therapeutic efficacy

Increased effectiveness of treatment through optimized delivery.

Dose dump

Premature drug release leading to potential overdose.

Intramuscular (IM) injection

Administers 2-5 ml into large muscle groups.

Subcutaneous (SC) injection

Administers 1-2 ml into fatty tissue.

Immunogenicity

Ability of substances to provoke immune responses.

Cyclodextrins

Carbohydrates forming complexes to enhance drug solubility.

Inclusion complex

Complex where drug is encapsulated within cyclodextrin.

Hydrophilic outer surface

Water-attracting exterior of cyclodextrin molecules.

Lipophilic central cavity

Fat-attracting interior of cyclodextrin for drug storage.

FDA approved derivatives

SBE-ß-CD and HP-ß-CD for parenteral use.

Long-term toxicity

Assessment of prolonged drug exposure effects.

Antigenic substances

Molecules capable of triggering immune reactions.

IgG1 levels

Immunoglobulin response measured after protein administration.

Prolonged release benefits

Useful for diabetes, cancer, contraception, osteoporosis, arthritis.

Volume of IM injection

Typically between 2-5 ml for effective delivery.

Volume of SC injection

Typically between 1-2 ml for effective delivery.

Safety in injections

Avoiding veins/arteries requires trained personnel.

Molecular rigidity

Structural inflexibility affecting cyclodextrin solubility.

Hydrogen bonding

Intermolecular forces impacting cyclodextrin crystal state.

Hydrogen Bond

Attraction between hydrogen and electronegative atoms.

βCD

Beta-cyclodextrin, has complete secondary belt structure.

Solubility of βCD

Approximately 18 mg/ml in water.

Sulfobutyl Ether βCD

Modified βCD with solubility over 1200 mg/ml.

αCD

Alpha-cyclodextrin, has incomplete hydrogen bond belt.

γCD

Gamma-cyclodextrin, features non-coplanar structure.

Cyclodextrin Advantages

Improves solubility, bioavailability, and stability.

Tissue Irritation Reduction

Minimizes discomfort from drug administration.

Odor Masking

Conceals unpleasant smells of drugs.

Voriconazole

Antifungal drug using SBE7-β-CD for IV administration.

Ziprasidone

Antipsychotic drug using SBE7-β-CD for IM administration.

Aripiprazole

Antipsychotic drug using SBE7-β-CD for IM administration.

Telavancin

Infection treatment using HP5-β-CD for IV administration.

Oily Vehicles

Used for modified release parenteral products.

Isopropyl Myristate

Synthetic fatty acid ester alternative vehicle.

Ricinoleic Acid

High content fatty acid in castor oil.

Esterification

Process to create long-chain fatty acid drug derivatives.

Hydrolysis

Chemical breakdown of esters to release parent drug.

Autoxidation

Degradation of unsaturated fatty acids by heat/light.

Oil/Water Partition Coefficient

Influences drug absorption rate in formulations.

Aqueous Suspension

Saturated solution with suspended drug particulates.

Paliperidone Palmitate

Prodrug formulation of paliperidone for IM injection.

Invega Sustenna

Injection formulation given every 28 days.

Testosterone Undecanoate

Long-acting depot formulation in castor oil.

Log P

Measure of drug's hydrophobicity; higher means less soluble.

Therapeutic Action Duration

Lasts from one week to one month.

CABENUVA

Cabotegravir and rilpivirine injectable suspension for HIV.

Initial Approval

First U.S. approval in 2021 for CABENUVA.

HIV-1 RNA Concentration

Measured in copies per mL; targets <50 copies.

FDA Snapshot Algorithm

Method to assess treatment outcomes in HIV patients.

Formulation Parameters

Factors affecting therapeutic benefit of drug formulations.

Particle Size

Influences drug absorption and therapeutic efficacy.

Crystal Habit

Refers to the geometric shape of drug crystals.